PROMIZING — Proportional-Assist vs Pressure-Support Ventilation

1. Publication

• Title: Proportional-Assist Ventilation for Minimizing the Duration of Mechanical Ventilation
• Acronym: PROMIZING
• Year & Journal: New England Journal of Medicine, published online June 13, 2025 (print: 2025;393(11):1088-1103)
• Citation: Bosma KJ, Burns KEA, Martin CM, et al; PROMIZING Study Investigators, the Canadian Critical Care Trials Group, and the REVA Network. Proportional-Assist Ventilation for Minimizing the Duration of Mechanical Ventilation. N Engl J Med. 2025;393(11):1088-1103. doi:10.1056/NEJMoa2505708

2. Context & Rationale

Background: Pressure-support ventilation (PSV), the standard mode for facilitating liberation from mechanical ventilation, delivers a fixed pressure assist regardless of the patient's actual respiratory drive — potentially causing over-assistance and misleading clinicians about extubation readiness. Proportional-assist ventilation with load-adjustable gain factors (PAV+) delivers pressure assistance proportional to the patient's instantaneous inspiratory effort, a more physiologically coherent approach, but smaller trials over ~30 years had not shown a significant liberation benefit.

Research Question/Hypothesis: In critically ill adults on mechanical ventilation ≥24 hours, does PAV+ reduce the time to successful liberation from mechanical ventilation compared with PSV?

Why This Matters: PROMIZING was designed as the largest, most definitive test of a physiologically appealing ventilation mode that had repeatedly failed to demonstrate benefit in smaller trials — a genuine test of whether the theoretical advantage translates to a hard clinical endpoint at scale.

3. Design & Methods

• Study Type: International, randomized, open-label, multicenter clinical trial
• Setting & Centers: Multiple centers, Canada, France, Italy, Spain, Saudi Arabia (Canadian Critical Care Trials Group, REVA Network); 7-year enrollment period
• Population:
• Inclusion: Adult patients receiving mechanical ventilation ≥24 hours, able to undergo partial ventilatory support with PSV but not yet ready for liberation
• Exclusions: Not detailed in available trial text
• Intervention: PAV+ — targeting normal work of breathing
• Comparator: PSV — targeting normal respiratory rate and tidal volume
• Randomization: 573 critically ill adults
• Blinding: Open-label
• Statistical Power & Follow-Up: Primary outcome: time from randomization to successful liberation from mechanical ventilation (defined as ≥7 consecutive days off MV). Secondary: mortality, ventilator-free days, ICU/hospital discharge, reintubation rate, tracheostomy rate, adverse events, sedation use, delirium.

4. Key Results

573 patients randomized.

5. Internal Validity Assessment

• Randomization & Allocation: International, multicenter randomization across the Canadian Critical Care Trials Group and REVA Network sites; specific concealment mechanics not detailed in available trial text.
• Protocol Adherence & Separation: Clear physiological distinction between the two modes (PAV+ targeting work of breathing vs PSV targeting fixed respiratory rate/tidal volume) ensures genuine intervention contrast.
• Blinding & Detection Bias: Open-label (inherent to a ventilation-mode comparison); the primary outcome (time to successful liberation, defined by an objective ≥7-day threshold) is relatively resistant to detection bias.
• Missing Data & Sensitivity Analyses: Long, 7-year enrollment period across multiple countries suggests a challenging but ultimately completed recruitment process; specific missing-data handling not detailed in available trial text.
• Overall Internal Validity Conclusion: Strong — the largest and most rigorous test of PAV+ vs PSV to date, following ~30 years of smaller, inconclusive trials; the consistent null result across the primary outcome and nearly all secondary outcomes (except a modest delirium/sedation signal) provides high-confidence evidence resolving this long-standing question.

6. External Validity Assessment

• Population Representativeness: International, multicenter (Canada, France, Italy, Spain, Saudi Arabia) mechanically ventilated ICU population able to tolerate partial ventilatory support — broadly representative of general ICU weaning populations.
• Practice Context: PAV+ requires specific ventilator hardware/software capability not universally available; PSV is the near-universal default mode, making this a practical, real-world-relevant comparison.
• Overall External Validity Conclusion: Good — international, multicenter design supports broad generalizability to ICUs able to access both ventilation modes.

7. Strengths & Limitations

Strengths:

• Largest, most definitive PAV+ vs PSV trial to date, following decades of smaller, underpowered studies
• International, multicenter design (Canadian Critical Care Trials Group, REVA Network)
• Comprehensive secondary outcome assessment (mortality, reintubation, tracheostomy, sedation, delirium)
• Long-term commitment to a challenging, 7-year recruitment effort reflects rigorous trial conduct

Limitations:

• Open-label design (inherent to ventilation-mode comparison)
• Very long recruitment period (7 years) may introduce temporal practice-pattern heterogeneity
• The modest sedation/delirium benefit signal, while intriguing, was a secondary (not primary) outcome and requires cautious interpretation

8. Interpretation & Practice Impact

• Clinical Implications: Does not support routine adoption of PAV+ over standard PSV specifically to accelerate liberation from mechanical ventilation — the two modes produce statistically indistinguishable time-to-liberation outcomes.
• Mechanistic Coherence: The modest secondary signal favoring PAV+ on sedation use and delirium is biologically plausible (better patient-ventilator synchrony potentially requiring less sedation) but was not the primary hypothesis and needs confirmatory testing.
• Systems-Level Takeaway: ICUs need not prioritize PAV+ capability specifically for faster ventilator liberation, though the sedation/delirium signal may be worth further investigation as a secondary benefit domain.

9. Controversies & Subsequent Evidence

• Editorial Commentary/Debates: Presented at the Critical Care Reviews Meeting 2025 (CCR25) in Belfast as a major trial result; independent commentary (PulmCCM "Results from CCR25") summarized the finding succinctly as PAV+ not resulting in shorter liberation time than PSV among 573 patients.
• Guideline Integration: Resolves ~30 years of smaller, inconclusive PAV+ trials with a definitive null result on the primary liberation-time question, likely to temper enthusiasm for PAV+-specific hardware investment purely for weaning-acceleration purposes.

10. Summary & Executive Takeaway

Summary: PROMIZING, an international multicenter trial recruiting over 7 years, randomized 573 mechanically ventilated adults to PAV+ or PSV. Time to successful liberation from mechanical ventilation, mortality, ventilator-free days, and most other outcomes showed no significant difference, though PAV+ showed a modest secondary signal toward less sedation use and delirium.

Overall Takeaway: After decades of physiologically appealing but inconclusive smaller trials, this large, definitive study confirms that PAV+ does not accelerate liberation from mechanical ventilation compared with standard PSV — though a modest sedation/delirium benefit signal may warrant further investigation as a distinct potential advantage.

11. Bibliography

• Bosma KJ, Read BA, Bahrgard Nikoo MJ, et al. A pilot randomized trial comparing weaning from mechanical ventilation on pressure support versus proportional assist ventilation. Crit Care Med. 2016;44(6).
• Bosma KJ, Martin CM, Burns KEA, et al. Study protocol for PROMIZING. Trials. 2023;24(1):232.